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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
After an organ or stem cell transplant, the drugs that stop rejection also stop the immune system from policing Epstein-Barr virus, and infected B cells can grow into a lymphoma. The first move is to ease the immunosuppression; then the antibody rituximab, chemotherapy if needed, and, newest of all, off-the-shelf virus-specific T cells that restore the missing immune control.
PTLD spans a spectrum from EBV-driven polyclonal hyperplasia to monomorphic lymphoma (usually diffuse large B-cell, sometimes Burkitt, plasmablastic, T-cell or Hodgkin-like), classified under WHO 2022 as lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation. EBV is detectable in most early and paediatric cases and about half of late adult cases; EBV-negative PTLD arises later and behaves like de novo lymphoma. Risk is driven by the degree of T-cell suppression (T-cell-depleting induction, tacrolimus-based regimens), EBV-seronegative recipients of seropositive organs (the paediatric scenario), and organ type. In allogeneic stem cell transplant the risk factors are T-cell depletion, mismatched or cord blood donors and anti-thymocyte globulin.
Management is stepwise. Reduction of immunosuppression is the first intervention and alone induces remission in a minority, at the cost of rejection risk. Rituximab monotherapy follows for CD20-positive disease; the PTLD-1 trial (Trappe and colleagues, Lancet Oncology 2012) established sequential therapy with four doses of rituximab followed by CHOP, and its risk-stratified successor (JCO 2017) showed that patients in complete remission after rituximab can continue rituximab alone, reserving CHOP for the rest. Surgery or radiotherapy handles localised disease, and EBV DNA monitoring with pre-emptive rituximab is standard after high-risk stem cell transplants. The newest treatment restores what was lost: EBV-specific cytotoxic T cells. Tabelecleucel (Ebvallo), an allogeneic, HLA-matched, off-the-shelf EBV-specific T-cell product, received European approval in December 2022 for relapsed or refractory EBV-positive PTLD after at least one prior therapy, on the basis of the ALLELE study; in the United States it received a complete response letter in January 2025 tied to manufacturing inspection findings and it does not yet appear on the FDA list of approved cellular and gene therapy products, so US patients access EBV-specific T cells through trials and academic programmes. CD19 CAR-T and bispecific antibodies have been used in small numbers of refractory patients.
| Setting | Approach | Guideline |
|---|---|---|
| All PTLD, first step | Reduce immunosuppression as far as graft safety allows, with close monitoring for rejection; surgery or radiotherapy for localised disease. | not mapped |
| CD20-positive PTLD not responding to reduced immunosuppression | Rituximab weekly for four doses; patients in complete remission continue rituximab consolidation alone, others proceed to R-CHOP (PTLD-1 risk-stratified sequential treatment). | NCCN Category 2A |
| EBV-positive, relapsed or refractory | EBV-specific T cells: tabelecleucel (EMA approval 2022; under FDA review) or institutional virus-specific T-cell programmes; clinical trials. | not mapped |
| After allogeneic HSCT, high risk | Weekly plasma EBV DNA monitoring with pre-emptive rituximab when load rises; reduction of immunosuppression where possible. | not mapped |